Alpha-1 Antitrypsin Deficiency: Does Increased Neutrophil Adhesion Contribute to Lung Damage?

Alpha-1 antitrypsin deficiency (AATD) arises from alpha-1 antitrypsin (AAT) antiprotease mutations. The Z allele (Glu342Lys point mutation) is the most common variant that leads to disease manifestation (homozygous PiZZ state). Misfolded Z-AAT polymerizes within cells, causing endoplasmic reticulum (ER) stress, and a low circulating concentration of functional AAT means that the proteolytic action of neutrophil-derived serine proteases is unopposed. There is much to learn about the development and progression of AATD; the evidence is accumulating that the lack of AAT may have additional proinflammatory or immunomodulatory effects.